Unrelated blogger comments July 2017

U
Last month more Eagles were landing. 
Will there be a new one this month or will it get run over.   


Do the EMA say yes to ocrelizumab in PPMS? 
The FDA said yes, what’s the hold up


Do they say no to ocrelizumab in PPMS?
If is obviously doing something


Do they say yes to active PPMS? 
Have they convinced the regulators that it is not simply the people with active PPMS.  Have they done enough to address this?


However if you want to say something that is unrelated to any these issues this is the place for you.


About the author

MouseDoctor

55 comments

  • "Do they say yes to active PPMS?
    Have they convinced the regulators that it is not simply the people with active PPMS. Have they done enough to address this?"

    How would the regulators really know the differences between "active PPMS" and "non active PPMS"? Isn't that a neuro concept – how on earth would a FDA/TGA/other body beaurocrat know about any of these issues? Is it because neuros have butchered the MS field by dividing it into illogical and phenotypes? A while ago I read some piece that blamed pharma for the MS phenotypes but pharma do what suits pharma. neuros are the ones that swear by the hippocritical oath…

    • It is a rituximab me-too, surely in this day and age we should be using humanised or human anti CD20. However it,ll work

  • What about possible danger of taking simvastatin to pwMS having an already low cholesterol level? My 'natural' total cholesterol measure is 3.1 and my GP has advised against me taking any statins. We tried a dose of 10mg/day for a month and it fell to 2.7, which he said was entering the zone of increased cancer risk. I have since stopped taking it. It seems to me that pwMS already with low cholesterol can't benefit from this potential route to decreasing MS accelerated brain atrophy, but then, depending on simvastatin's mode of action, perhaps we don't need to.

    Richard S

  • Any thoughts on the use of Human Growth Hormone to help maintain muscle function in MS?
    Or any other benefit HGH may have?

  • If you deplete incoming peripheral B-cells with any of the current B-cell therapies, does this have any effect on the EBV controlled memory B-cells in follicles in the brain?

    In other words, does current B-cell therapies halt or diminish the size or function of these EBV driven memory B-cell follicles or diminish the size/function by depleting incoming B-cells or do current B-cell therapies have no effect on EBV driven memory B-cells in the brain that could possibly be driving MS?

    • Maybe not alemtuzumab does not affect OCB. It does get into the CNS in sufficient ammounts and or does not have the machinery to deplete CNS B cells.

      Cladribine may get into CNS but does enough get in?

    • "If you deplete incoming peripheral B-cells with any of the current B-cell therapies, does this have any effect on the EBV controlled memory B-cells in follicles in the brain?"

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4689808/

      "A number of factors may limit a more robust effect of peripheral B cell depletion on progressive MS biology. Meningeal immune cell aggregates in which B cells can be a prominent feature may not be as efficiently targeted by anti-CD20 antibodies that only weakly penetrate the CNS. It is also possible that long-lived plasma cells (that do not express CD20) and the antibodies they generate may play a more important role in progressive forms of MS compared to relapsing MS."

  • https://www.ncbi.nlm.nih.gov/pubmed/22968102

    "TNF blockade augmented B cell activation as reflected by the expression of early activation markers, CD40, and costimulatory molecules, without affecting differentiation towards plasmablasts. This was associated with a specific increase of the unswitched fraction of circulating memory B cells and a decreased level of somatic hypermutation in anti-TNF treated patients, indicating an impairment of the germinal centre-dependent B cell maturation."

    • And anti-TNF therapy has been associated with the development/exacerbation of clinically silent of MS in some of those receiving this therapy.

    • OK, I admit it sounds tempting in a 'what have I got to lose?' kind of way. Something turns me off 'food supplements' big time though, I'm a big believer in eating the food we've evolved to eat and not to mess with it. And you're right of course, why such a mega dose? Thanks MD for explaining how these things work (below). £££££ 😉

    • Not messing with it will probably work if you're a healthy baseline human, but when you have a serious degenerative disease, messing with the body is very important; it's the whole premise of medicine.

      Always weigh the risk of medicines against the risk of not taking the medicine, i.e unabated progression of your illness.

    • Would like to ask Mouse Dr, what does this means:

      "This study provides Class I evidence that for patients with SPMS, LA
      reduces the rate of brain atrophy"

    • Anon 1.03 Believe me I'm not risk averse at all when it comes to evidence based medicines but if I was to jump on every quasi vitamin tonic bandwagon going I'd be rattling!

    • I liked it!

      I have RRMS (one hour the docs say that I have RRMS another time I am still CIS, at last I started treatment for MS soon to the first and only outbreak so far, there are exact 03 years and 4 months). I take Alpha lipoic acid but at the usual dose of 300 mg per day (1 tablet), and alternate to the use of Creatine, Coenzyme Q-10 and Cysteine, which is an alternative to try not to overload the kidneys and liver, and I use them because I still play sports, I practice bodybuilding with intensity.

      Let's see what will happen…

    • We dont know because they did not do a dose-response and your dose is ten times less than was tested. If pharma was doing these trials they are made to do a dose-response yet when academics do them it is OK not to do this. The problem is you don't know what the minimum safe dose is. The MS-STAT2 trial is doing only one dose at 80mg but surely on should ask what is the the standard low dose doing, because statins are not inert and it is known that high doses cause side effects. Hopefully they wont do a 5 year trial and then the regulators say but you didn't prove that this was the minimally effective dose, go away and do it again.

      They wont do it an extra arm means anoth 600 people and a few million, but should we be supporting half-cocked trials. The Lipoic acid trial is another example a trial of hopelessly underpowered, which no-one in the the professional circle will take much notice off saying the evidence is not good enough, we will have a gaggle of these types of trial and stuff goes nowwhere.

    • why aren't they doing it…simple reason is cost. Adding extra arms raises the cost above the threshold at which funders can fund.

    • So I'm back to my usual rationale – my dose obviously doesn't do any harm and may be doing some good (cf Co Q-10 etc.) – not really how you would choose to treat a condition, but I'll take what I can get – thanks for your input, MD, very insightful, and Luis for posting the link – great community work as usual.

    • It certainly was for you, Luis, I wouldn't know half the things I do without this blog and its contributors.

      Good luck with your hsct, hope it all goes well for you

    • On Jul 9, 2017, at 5:26 PM, "varatojo@sapo.pt" wrote:

      Hello a Dr,Spain my name is Luis i´m 47 years old ,i am from portugal i have ms

      Have reead your study "Lipoic acid in secondary progressive MS"

      And would like to know :

      Why have´nt you did also in rrms patients since ms is a neurodegenerative disease from the start?

      Regarding the daily dose of 1200mg how you came about that number?

      Given the excellent results of the study how did the ms comunity react?

      Thank you so much

      Luis Fernando

    • Dear Mr. Fernando,

      Thank you for your interest in my work. I certainly would expect that lipoic acid could work in RRMS for exactly the reasons you gave. I did not have funding to do that trial so limited it to SPMS.

      1200 mg was equivalent to the dose found effective in the mouse model of MS.

      So far the MS community has been enthusiastic. I have funding to conduct a larger trial to see if lipoic acid has a clinical benefit on walking and overall neurological exam. Stay tuned!

      Best wishes for your health,

      Rebecca Spain

    • I've come to this late this month – thanks for the info Luis and MD.
      I've found via a google search the following: 'there is no official recommended daily allowance for ALA: however, the study in Diabetes Care suggested on oral dose of 600mg a day provided the best risk-to-benefit ratio for combating peripheral neuropathy'
      So maybe I'll add it to my supplement intake – as you so aptly put it Luis – 'what do I have to lose'
      Best wishes with the hsct

    • Thanks Fi
      Conclusions—Subjects taking 1200 mg of LA from two of the three oral formulations achieved
      serum Cmax and AUC levels comparable to that observed in mice receiving 50 mg/kg SC dose of
      LA, which is a highly therapeutic dose in EAE. 1200 mg oral LA can achieve therapeutic serum
      levels in MS subjects.

      https://www.ncbi.nlm.nih.gov/pubmed/20150394

  • "we will have a gaggle of these types of trial and stuff goes nowwhere."
    With all due respect an spms person with ms in a wheel chair does´nt goes nowwhere also
    So its that "what do i have to loose" situation we ms´ers are face from time to time (and time is brain)
    Luis

    • Luis, you've got it in one there. I know someone in that exact situation taking 80mg simvastatin and know of (but don't know personally) a few heading abroad for HSCT. Thanks for posting all the research links you do, much appreciated.
      ps I recall you sharing some HSCT info before and thanking you then. I'm in disguise today!

    • And it's so frustrating that maybe the solution is just sitting there and won't be found because it will cost too much – and not provide enough profit.

  • Anti-lingo 1 will work if administered intrathecally. Why would they try and administer an agent which cannot pass the BBB intravenously? Yes, I know that in mice a tiny percentage (<0.07%) of the drug managed to pass the BBB if administered intravenously but mice aren't humans.

    The trial would have been successful if they administered it intrathecally in massive doses. Why does pharma actively attempt to force its trials to fail?

    • Sorry they publishers changed the date to the 6th and it came a week early

      http://multiple-sclerosis-research.blogspot.com/2017/07/a-potential-new-treatment-for-spasticity.html

      BMS204352, which we used in this study is a proven neuroprotector and limits nerve loss after brain and spinal cord trauma. It went into a trial in stroke but failed, but they all fail in stroke because people don't get the drug quick enough, MS is different because one can be taking drug before the event occurs. However the stroke study shows the drug target is safe as the trial was over one thousand people. Will VSN16 be neuroprotective, we are on the case

  • Re.. NHS England has announced plans to stop doctors prescribing homeopathy, herbal and other "low value" treatments. Is in the news.

    This includes Lidocaine plasters for treating nerve-related pain, I know some pwMS use these.

  • As a person with MS I have experienced people who are aware I have MS making incorrect assumptions about my abilities and knowledge. This has been frustrating at times. Challenging assumptions is key to innovation.

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